This study is being done to see if adding nivolumab to radiation therapy and bevacizumab can increase the effectiveness of the treatment for recurrent glioblastoma.

Inclusion Criteria:

• Histologic confirmed glioblastoma (WHO grade IV), IDH wildtype confirmed by DNA sequencing

• MGMT hypermethylation in archival tumor biopsy, determined by any CLIAapproved, DNA-based assay

• Prior maximal feasible surgical resection of biopsy

• Prior treatment with radiation and temozolomide chemotherapy

• Pathologic and/or Radiographic evidence of recurrent disease

• Circumscribed enhancing tumor ≤ 5.0 cm in largest diameter (T1 post contrast)

• 1 prior course of radiation therapy

• Age ≥ 18 years

• Karnofsky performance status ≥ 70% or ECOG 0 or 1

• Adequate bone marrow function

  • Hemoglobin ≥ 10g/dL
  • Absolute neutrophil count ≥ 1,500/mm 3
  • Absolute lymphocyte count ≥ 200/mm 3
  • Platelet count ≥ 100,000/mm3

• Adequate liver function

  • Bilirubin <1.5 times upper limit normal (ULN)
  • AST and ALT ≤ 3 times ULN
  • Alkaline phosphatase ≤ 2 times ULN

• Adequate renal function

  • BUN and Creatinine <1.5 times ULN

Exclusion Criteria:

• Infratentorial location of the recurrence
• IDH mutated glioblastoma
• More than one prior tumor recurrence after standard first-line therapy
• Prior radiation to the brain within ≤ 4 months
• Circumscribed enhancing tumor >5.0 cm in largest diameter (T1 post contrast)
• Pulmonary embolus or deep vein thrombosis within preceding 2 months
• Grade 2 or greater congestive heart failure
• Unstable angina, myocardial infarction within past 12 months
• Peptic ulcer, abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within past 6 months
• Nonhealing wound, ulcer or bone fracture
• Prior spontaneous CNS hemorrhage (as determined from clinical history, CT, or MRI)
• Uncontrollable hypertension
• Requiring escalating or chronic supraphysiologic doses of corticosteroids (> 4 mg dexamethasone daily) for control of disease at the time of registration
• Previous or current treatment with an anti-CTLA-4, anti-PD-1, anti-PD-L1, or anti-PDL2 agent.
• Previous or current treatment with bevacizumab
• Hypersensitivity to nivolumab or bevacizumab or any of its excipients
• Diagnosis of immunodeficiency, including Human Immunodeficiency Virus (HIV) or acquired immunodeficiency syndrome (AIDS)
• Known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
• Known history of active TB (Bacillus Tuberculosis)
• Known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
• Active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• Known history of, or any evidence of active, non-infectious pneumonitis.
• Active infection requiring systemic therapy.
• Pregnancy or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
• Unable to undergo MRI of the brain (i.e. pacemaker or any other contraindication for MRIs).